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Integrative genetic analysis of alcohol dependence using the GeneNetwork Web resources.

Williams RW, Lu L - Alcohol Res Health (2008)

Bottom Line: And the list of candidate genes keeps growing.However, just compiling lists of such genes is not satisfying.This article summarizes some of the challenges associated with generating this understanding and presents a Web-based resource that may aid researchers in better understanding the mechanisms through which alcohol acts on the body and how different genes influence this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee.

ABSTRACT
Not long ago, the idea that alcoholism had a genetic basis-even in part-was highly controversial (Goodwin 1971, 1975). Over the past 35 years, however, the contribution of genetic factors has become conventional wisdom. This change to a large extent results from compelling experimental studies utilizing inbred and recombinant inbred (RI) strains of rats and mice (e.g., Crabbe et al. 1983; Crabbe 1983; McClearn 1972). Over the last decade, the focus of genetic research in the alcohol field has shifted away from epidemiological and statistical estimates of alcoholism heritability to molecular studies of single gene variants that have explanatory, predictive, and even therapeutic utility. Large-scale genetic studies such as the Collaborative Study on the Genetics of Alcoholism (COGA) have highlighted variations (i.e., polymorphisms) in numerous genes that are related to alcohol use, abuse, and risk of dependence (for a review, see Edenberg and Foroud 2006). And the list of candidate genes keeps growing. However, just compiling lists of such genes is not satisfying. What is needed is an in-depth understanding of how DNA variants cause differences in alcohol dependence, especially in the context of a myriad of environmental contributing factors, such as diet, stressors, and previous drinking history. This article summarizes some of the challenges associated with generating this understanding and presents a Web-based resource that may aid researchers in better understanding the mechanisms through which alcohol acts on the body and how different genes influence this process.

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Related in: MedlinePlus

A genetic map of Gabra1 expression in a brain region called the hippocampus of mice from the BXD family of recombinant inbred strains. The x-axis lists mouse chromosomes 1 through X. The y-axis provides a measure of linkage (LRS = likelihood ratio statistic) between variation in Gabra1 expression and each part of the mouse genome. A prominent peak on chromosome 11 provides strong confirmation that sequence differences near the Gabra1 gene (which is located on that chromosome) control Gabra1 expression. Secondary peaks on chromosomes 5 and 16 suggest that DNA sequences in those regions likely also modulate expression of the Gabra1 mRNA.
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f19-arh-31-3-275: A genetic map of Gabra1 expression in a brain region called the hippocampus of mice from the BXD family of recombinant inbred strains. The x-axis lists mouse chromosomes 1 through X. The y-axis provides a measure of linkage (LRS = likelihood ratio statistic) between variation in Gabra1 expression and each part of the mouse genome. A prominent peak on chromosome 11 provides strong confirmation that sequence differences near the Gabra1 gene (which is located on that chromosome) control Gabra1 expression. Secondary peaks on chromosomes 5 and 16 suggest that DNA sequences in those regions likely also modulate expression of the Gabra1 mRNA.

Mentions: Similarly, the tools available on the GeneNetwork Web site allow investigators to verify that the observed differences in expression actually are caused by sequence variants in or near the Gabra1 gene by determining which area of the mouse chromosomes is associated with variation of mRNA expression (see figure 19). These analyses found that the greatest association between a chromosomal region and Gabra1 mRNA expression existed for a region on chromosome 11 that corresponds precisely to the location of Gabra1; additional findings confirmed the validity of this result.


Integrative genetic analysis of alcohol dependence using the GeneNetwork Web resources.

Williams RW, Lu L - Alcohol Res Health (2008)

A genetic map of Gabra1 expression in a brain region called the hippocampus of mice from the BXD family of recombinant inbred strains. The x-axis lists mouse chromosomes 1 through X. The y-axis provides a measure of linkage (LRS = likelihood ratio statistic) between variation in Gabra1 expression and each part of the mouse genome. A prominent peak on chromosome 11 provides strong confirmation that sequence differences near the Gabra1 gene (which is located on that chromosome) control Gabra1 expression. Secondary peaks on chromosomes 5 and 16 suggest that DNA sequences in those regions likely also modulate expression of the Gabra1 mRNA.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860492&req=5

f19-arh-31-3-275: A genetic map of Gabra1 expression in a brain region called the hippocampus of mice from the BXD family of recombinant inbred strains. The x-axis lists mouse chromosomes 1 through X. The y-axis provides a measure of linkage (LRS = likelihood ratio statistic) between variation in Gabra1 expression and each part of the mouse genome. A prominent peak on chromosome 11 provides strong confirmation that sequence differences near the Gabra1 gene (which is located on that chromosome) control Gabra1 expression. Secondary peaks on chromosomes 5 and 16 suggest that DNA sequences in those regions likely also modulate expression of the Gabra1 mRNA.
Mentions: Similarly, the tools available on the GeneNetwork Web site allow investigators to verify that the observed differences in expression actually are caused by sequence variants in or near the Gabra1 gene by determining which area of the mouse chromosomes is associated with variation of mRNA expression (see figure 19). These analyses found that the greatest association between a chromosomal region and Gabra1 mRNA expression existed for a region on chromosome 11 that corresponds precisely to the location of Gabra1; additional findings confirmed the validity of this result.

Bottom Line: And the list of candidate genes keeps growing.However, just compiling lists of such genes is not satisfying.This article summarizes some of the challenges associated with generating this understanding and presents a Web-based resource that may aid researchers in better understanding the mechanisms through which alcohol acts on the body and how different genes influence this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee.

ABSTRACT
Not long ago, the idea that alcoholism had a genetic basis-even in part-was highly controversial (Goodwin 1971, 1975). Over the past 35 years, however, the contribution of genetic factors has become conventional wisdom. This change to a large extent results from compelling experimental studies utilizing inbred and recombinant inbred (RI) strains of rats and mice (e.g., Crabbe et al. 1983; Crabbe 1983; McClearn 1972). Over the last decade, the focus of genetic research in the alcohol field has shifted away from epidemiological and statistical estimates of alcoholism heritability to molecular studies of single gene variants that have explanatory, predictive, and even therapeutic utility. Large-scale genetic studies such as the Collaborative Study on the Genetics of Alcoholism (COGA) have highlighted variations (i.e., polymorphisms) in numerous genes that are related to alcohol use, abuse, and risk of dependence (for a review, see Edenberg and Foroud 2006). And the list of candidate genes keeps growing. However, just compiling lists of such genes is not satisfying. What is needed is an in-depth understanding of how DNA variants cause differences in alcohol dependence, especially in the context of a myriad of environmental contributing factors, such as diet, stressors, and previous drinking history. This article summarizes some of the challenges associated with generating this understanding and presents a Web-based resource that may aid researchers in better understanding the mechanisms through which alcohol acts on the body and how different genes influence this process.

Show MeSH
Related in: MedlinePlus